Human immunodeficiency virus (HIV) enters target cells by specific interactions between the viral envelope proteins gp41 and gp120 and human target cell receptors. The long term goal of this project is to discover small, drug-like, molecules that disrupt HIV entry by binding to viral envelope or human target cell receptor proteins. The specific aims are: Specific Aim 1: Develop the pseudo typing assay of HIV envelope-mediated viral entry for application to high throughput screening (HTS) of small drug-like molecules by robotic systems. Specific Aim 2: Extend the HIV entry assay for discrimination between small molecule inhibitors that bind to HIV envelope proteins, from small molecule inhibitors that bind to human target receptor proteins.